Cross-linked polymer gel materials are widely utilized in the biomedical industry. For example, polysaccharide gels have been applied in contact lenses, blood contact materials, controlled release formulations, wound dressings, bioadhesives, membranes, superabsorbents, cell encapsulation and immunoisolation materials, and tissue engineering scaffolds.
The potential use of polysaccharide gel materials for treating damaged heart tissue has been intensively researched during the past decade.
The main focus of research has been on utilizing polysaccharide gels for treating the heart tissue following myocardial infarction. Myocardial infarction typically causes an acute loss of myocardial tissue and an abrupt increase in loading conditions which induces left ventricular remodeling. The early phase of left ventricular remodeling involves expansion of the infarct zone, which often results in early ventricular rupture or aneurysm formation. Late remodeling encompasses the entire left ventricle and involves time-dependent dilatation, recruitment of border zone myocardium into the scar, distortion of ventricular shape and mural hypertrophy. Consequently, it may lead to progressive deterioration in contractile function, heart failure and eventually death.
Accordingly, cessation or reversal of progressive chamber remodeling is an important aim of heart failure therapy. Clinical attempts to minimize the devastating effects of myocardial infarction have thus far failed to effectively repair the irreversible damage inflicted to the heart tissue.
Recently, attempts to implant living cells in damaged myocardium have given hope for repairing the damaged tissue via promoting tissue regeneration. This approach has advanced considerably with the development of 3-D biomaterial scaffolds aimed at supporting implantation of donor cells (e.g., cardiac cells or stem cells) in the myocardium. Lately, 3-D biomaterial scaffolds made of polysaccharide gel were successfully implanted onto damaged myocardium with promising results. However, clinical use of such cell seeded 3-D biomaterial scaffolds is limited due to scarcity of suitable donor cells and the high risk involved in major surgery.
One polysaccharide gel that has been investigated for treating damaged tissue is a partially cross-linked aqueous soluble formulation of sodium alginate and calcium cations. The partially cross-linked alginate solution may undergo a transition from liquid to gel in damaged body tissue with slightly elevated extracellular calcium concentration, thereby mechanically supporting the tissue. One particular application is for the treatment of tissue damaged by myocardial infarction, in which case the partially cross-linked alginate solution gels in the infarcted cardiac tissue and supports the weakened heart wall to prevent cardiac remodeling and subsequent congestive heart failure.
However, there is a need to provide improved processes for the manufacturing of injectable partially cross-linked alginate solutions that maintain a liquid state until they interact with damaged tissue.